We are studying simian virus 40 (SV40), a monkey polyomavirus, which was an accidental contaminant of poliovirus vaccines and other vaccines administered in 1955-62. This widespread population exposure to SV40 has raised concern, because SV40 causes cancer in laboratory rodents and because some researchers, though not all, have identified SV40 DNA sequences in human tumor tissues, including mesothelioma, brain tumors, and NHL. We are examining the association between SV40 and human cancers in two ways. First, we are conducting retrospective follow-up studies of cohorts exposed to SV40-contaminated vaccines. In Denmark, where SV40-contamination of poliovirus vaccine was well-documented, we have used cancer registry data to examine cancer incidence in birth cohorts with varying vaccine exposure. Similarly, to look at the effect of SV40 on NHL risk, we are presently examining NHL incidence among persons with AIDS in the U.S. as a function of birth year (which serves as a surrogate for poliovirus vaccine exposure), using data from the AIDS Cancer Match Registry study. Finally, we are following up 600,000 U.S. Army recruits from 1959-61, some of whom received an SV40-contaminated adenovirus vaccine, for the occurrence of mesothelioma, brain tumors, and NHL. Second, we are utilizing biological specimens to study the link between SV40, vaccine exposures, and cancer. We recently looked for SV40 DNA sequences in brain tumors from northern India, where SV40 infection in humans may occur through contact with infected rhesus macaques. In an ongoing study, we are working with the Collaborative Perinatal Project, a cohort study of 54,000 pregnant women and their subsequently born children (enrolled 1959-66). In that context, we are studying whether SV40-seroconversion during pregnancy was associated with receipt of poliovirus vaccine and whether children born to SV40-seroconverting mothers had increased cancer risk.